Focal Facial Dermal Dysplasia 1, Brauer Type

Description

The focal dermal dysplasias (FFDDs) are a group of related developmental defects characterized by bitemporal or preauricular skin lesions resembling aplasia cutis congenita. Cervantes-Barragan et al. (2011) proposed a classification of FFDD in which there are 4 subtypes. FFDD1 (Brauer syndrome) is characterized by temporal skin depressions that resemble 'forceps marks.' Other facial anomalies, comprising sparse lateral eyebrows, distichiasis, and a flattened nasal tip, are usually mild. Inheritance is autosomal dominant. FFFD2 (Brauer-Setleis syndrome; 614973) is characterized by bitemporal skin lesions with variable facial findings, including thin and puckered periorbital skin, distichiasis and/or absent eyelashes, upslanting palpebral fissures, a flat nasal bridge with a broad nasal tip, large lips, and redundant facial skin. Inheritance is autosomal dominant. FFDD3 (Setleis syndrome; 227260) is characterized by the same facial features as FFDD2, but the inheritance is autosomal recessive. FFDD4 (614974) is characterized by isolated, preauricular skin lesions with autosomal dominant or recessive inheritance (summary by Slavotinek et al., 2013).

Genetic Heterogeneity of Focal Facial Dermal Dysplasia

FFDD3 (227260) is caused by mutation in the TWIST2 gene (607556) on chromosome 2q37. FFDD4 (614974) is caused by mutation in the CYP26C1 gene on chromosome 10q23.

Clinical Features

Brauer (1929) described 38 patients with this condition and traced it through 5 generations of a family in which 155 persons were said to have been affected. The affected progenitor was said to be one Johann Jokeb Van Bargen, who migrated to Germany from Holland in the 16th century. The resemblance to 'forceps marks' was noted. Unilateral occurrence was described in 2.

Affected persons in 5 generations of an English family were described by Jensen (1971).

McGeoch and Reed (1971, 1973), who studied an Australian family with many affected members of many generations, called the disorder focal facial dermal dysplasia. Although the main finding was a wrinkling or puckering of the skin at the temples, some patients showed guttate areas on the lateral aspects of the chin and midforehead. Histologically, the lesion is a mesodermal dysplasia with near absence of subcutaneous fat and with skeletal muscle almost contiguous with epidermis. The puckered skin is well accounted for by the hypoplasia of the corium and lack of fat.

Magid et al. (1988) described a sporadic case in a Mexican-American male infant.

Inheritance

Father-to-son transmission was observed in the 3 large kindreds (German, English, Australian) with Brauer syndrome reported by Brauer (1929), Jensen (1971), and McGeoch and Reed (1971, 1973), indicating autosomal dominant inheritance.

History

Kowalski and Fenske (1992) proposed a classification in which Brauer syndrome was referred to as FFDD type I. They suggested that Setleis syndrome (focal facial dermal dysplasia with additional features) is a separate entity, which they classified as FFDD type III. They designated an autosomal recessive form of FFDD without additional features as FFDD type II; they reported a family with FFDD type II and found 1 other similar family (family 'M' of Jensen, 1971). Cervantes-Barragan et al. (2011) classified the FFDD phenotype in the sibs reported by Kowalski and Fenske (1992) as FFDD4 (614974).